crossing96/oncoscreening huggingface dataset:
Four novel biomarkers for bladder cancer identified by weighted gene coexpression network analysis.	Bladder cancer (BC) is one of the most malignancies in terms of incidence and recurrence worldwide. The aim of this study is to find out novel and prognostic biomarkers for patients with BC. First, we identified 258 differentially expressed genes by using GSE19915 from Gene Expression Omnibus database. Second, a total of 33 modules were identified by constructing a coexpression network by using weighted gene coexpression network analysis and yellow module was regarded as the key module. Furthermore, by constructing protein-protein interaction networks, we preliminarily picked out 13 genes. Among them, four hub genes (CCNB1, KIF4A, TPX2, and TRIP13) were eventually identified by using five different methods (survival analysis, one-way analysis of variance, the Spearman correlation analysis, receiver operating characteristic curve, and expression value comparison), which were significantly correlated with the prognosis of BC. The validation of transcriptional and translational levels made sense (based on Oncomine and The Human Protein Atlas database). Moreover, functional enrichment analysis suggested that all the hub genes played crucial roles in chromosome segregation, sister chromatid segregation, nuclear chromosome segregation, mitotic nuclear division, nuclear division, and organelle fission during cell mitosis. In addition, three of the hub genes (KIF4A, TPX2, and TRIP13) might be potential targets of cancer drugs according to the results of the genetical alteration. In conclusion, this study indicates that four hub genes have great predictive value for the prognosis of BC, and may contribute to the exploration of the further and more in-depth research of BC.	bladder
Three-dimensional histopathological reconstruction of bladder tumours.	BACKGROUND: Histopathological analysis is the cornerstone in bladder cancer (BCa) diagnosis. These analysis suffer from a moderate observer agreement in the staging of bladder cancer. Three-dimensional reconstructions have the potential to support the pathologists in visualizing spatial arrangements of structures, which may improve the interpretation of specimen. The aim of this study is to present three-dimensional (3D) reconstructions of histology images. METHODS: En-bloc specimens of transurethral bladder tumour resections were formalin fixed and paraffin embedded. Specimens were cut into sections of 4 μm and stained with Hematoxylin and Eosin (H&E). With a Phillips IntelliSite UltraFast scanner, glass slides were digitized at 20x magnification. The digital images were aligned by performing rigid and affine image alignment. The tumour and the muscularis propria (MP) were manually delineated to create 3D segmentations. In conjunction with a 3D display, the results were visualized with the Vesalius3D interactive visualization application for a 3D workstation. RESULTS: En-bloc resection was performed in 21 BCa patients. Per case, 26-30 sections were included for the reconstruction into a 3D volume. Five cases were excluded due to export problems, size of the dataset or condition of the tissue block. Qualitative evaluation suggested an accurate registration for 13 out of 16 cases. The segmentations allowed full 3D visualization and evaluation of the spatial relationship of the BCa tumour and the MP. CONCLUSION: Digital scanning of en-bloc resected specimens allows a full-fledged 3D reconstruction and analysis and has a potential role to support pathologists in the staging of BCa.	bladder
Chemosensitizer effect of cisplatin-treated bladder cancer cells by phenazine-5,10-dioxides.	We determined the chemosensitizer effect of phenazine dioxide derivatives to cisplatin and the possible mechanism of action on bladder cancer cells. Anti-proliferative activity of nine phenazine dioxide derivatives in presence or absence of cisplatin was evaluated in two bladder tumor human cells T24 and 253 J and one non tumor cell line V79-4. The sensitizer effect of the combined treatment was determined by chromosomal aberrations and micronucleus test. A possible mechanism of action of the sensitizer compounds as HDACi was also investigated.The phenazine dioxide 2c combined with cisplatin induced a cell cycle arrest on bladder cancer cells and resensitize the invasive and cisplatin resistant 253 J cell line. The HDAC inhibitory activity appears as one of the mechanism of action of the compound. The low toxicity levels against normal cells point out the phenazine dioxide derivative 2c as a very good scaffold for further design of HDACi sensitizer agents.	bladder
Low doses of decitabine improve the chemotherapy efficacy against basal-like bladder cancer by targeting cancer stem cells.	Low dose treatment with the DNA methylation inhibitor decitabine has been shown to be applicable for the management of certain types of cancer. However, its antitumor effect and mechanisms are context dependent and its activity has never been systematically studied in bladder cancer treatment. We used mouse models, cultured cell lines and patient-derived xenografts to demonstrate that low dose decitabine treatment remarkably enhanced the effects of cisplatin and gemcitabine on basal-like bladder cancer both in vivo and in vitro. Genetic lineage tracing revealed that the stemness of a bladder cancer stem cell population was inhibited by decitabine treatment in mice. These effects were accompanied by decreases in genome-wide DNA methylation, gene re-expression, and changes in key cellular regulatory pathways such as STAT3 signaling. These results indicate that this DNA-demethylating reagent is a promising therapeutic approach for basal-like bladder cancer treatment.	bladder
Gastrointestinal Stromal Tumor in a Patient with Neurofibromatosis Type 1 That Was Successfully Treated with Regorafenib.	An unconscious 55-year-old man with a history of neurofibromatosis type 1 (NF1) was transported to the emergency department and was diagnosed with acute renal failure owing to a large bladder tumor. A submucosal tumor was also identified in the duodenum. The patient was diagnosed with a primary gastrointestinal stromal tumor (GIST) of the bladder and duodenum. After six cycles of regorafenib therapy, (18)F-fluorodeoxyglucose accumulation in the duodenal GIST on positron emission tomography-computed tomography (PET-CT) showed a partial metabolic response. Currently, no standard drug therapy for unresectable or relapsed NF1-associated GIST has been established. Regorafenib may thus be considered as and appropriate initial therapy.	bladder
Impact of sex difference on survival of bladder cancer: A population-based registry data in Japan.	OBJECTIVE: To investigate the impact of sex on the prognosis of bladder cancer in Japan. METHODS: In total, 18 728 patients diagnosed as having bladder cancer from 1993 to 2006 were registered in population-based cancer registries of six prefectures in Japan. We estimated relative survival by sex, age, clinical stage at initial diagnosis and pathology. RESULTS: Patients included 14 203 men (75.8%) and 4525 women (24.2%). The stage at initial diagnosis in women was significantly higher than in men (P < 0.0001). Pathologically, women were more likely to have non-urothelial cancer than men (women 18.0%, men 9.5%, P < 0.0001). The 5-year relative survival was 80.3% for men and 67.7% for women. The 5-year relative survival was 93.0% for men and 87.7% for women in the localized cancer group, 34.8% for men and 23.9% for women in the locally advanced cancer group, and 7.1% for men and 8.3% for women in the metastatic cancer group. The relative survival of women was worse than that of men in the localized cancer group (hazard ratio 1.29, 95% confidence interval 1.05-1.57; P = 0.0145) and locally advanced cancer group (hazard ratio 1.32, 95% confidence interval 1.15-1.52; P = 0.0001), but not different in the metastatic cancer group (hazard ratio 1.04, 95% confidence interval 0.87-1.25; P = 0.6555). CONCLUSIONS: Population-based registry data in Japan show that the cancer stage at initial diagnosis is higher in women than in men, and women with localized or locally advanced bladder cancer have a worse prognosis compared with men.	bladder
Influence of laparoscopic access in cancer-specific mortality of patients with pTa-2pN0R0 bladder cancer treated with radical cistectomy.	INTRODUCTION AND OBJECTIVE: Minimally invasive surgery represents an attractive surgical approach in radical cystectomy. However, its effect on the oncological results is still controversial due to the lack of definite analyses. The objective of this study is to evaluate the effect of the laparoscopic approach on cancer-specific mortality. MATERIAL AND METHOD: A retrospective cohort study of two groups of patients in a pT0-2pN0R0 stage, undergoing open radical cystectomy (ORC) (n=191) and laparoscopic radical cystectomy (LRC) (n=74). Using Cox regression, an analysis has been carried out to identify the predictor variables in the first place, and consequently, the independent predictor variables related to survival. RESULTS: 90.9% were males with a median age of 65years and a median follow-up period of 65.5 (IQR27.75-122) months. Patients with laparoscopic access presented a significantly higher ASA index (P=.0001), a longer time between TUR and cystectomy (P=.04), a lower rate of intraoperative transfusion (P=.0001), a lower pT stage (P=.002) and a lower incidence of infection associated with surgical wounds (P=.04). When analyzing the different risk factors associated with cancer-specific mortality, we only found the ORC approach (versus LRC) as an independent predictor of cancer-specific mortality (P=.007). Open approach to cystectomy multiplied the risk of mortality by 3.27. CONCLUSIONS: In our series, the laparoscopic approach does not represent a risk factor compared to the open approach in pT0-2N0R0 patients.	bladder
Patients choose certainty over burden in bladder cancer surveillance.	BACKGROUND: Due to the high risk of recurrence of non-muscle invasive bladder cancer, all patients undergo regular cystoscopic surveillance for early detection. As cystoscopy is invasive, costly and increases the burden of the disease considerably, there is significant ongoing research and development into non-invasive urinary biomarker substitutes. This study aims to assess the level of sensitivity required before patients accept a new urinary biomarker. METHODS: We studied the preferences for a hypothetical diagnostic urinary biomarker and compared this to usual care (cystoscopy) at different levels of sensitivity among 437 patients with bladder cancer (354 men and 83 women) from the UK Bladder Cancer Prognosis Programme. A standard gamble approach was used to estimate the minimally acceptable sensitivity (MAS) of the new biomarker. Additionally, non-parametric statistical analyses were performed to investigate the association between surveillance preference and various patient characteristics. RESULTS: Almost half of patients (183, 43%) would not replace cystoscopy with a urinary biomarker unless it was 100% sensitive. The median MAS was 99.9999%, and nearly 85% of patients demanded a sensitivity of at least 99% before preferring a urinary biomarker test over cystoscopy. These results were consistent across all patient characteristics and demographic categories. CONCLUSIONS: Our results indicate that patients demand urinary biomarkers as sensitive as cystoscopy before they would be willing to forego cystoscopy for bladder cancer surveillance.	bladder
The Association of A Number of Predictive Factors for The Recurrence of Papillary Urothelial Neoplasm of Low Malignant Potential: Prognostic Analysis From Multiple Academic Centers.	PURPOSE: To identify clinically useful predictors for the recurrence of papillary urothelial neoplasm of low malignant potential (PUNLMP), we reviewed the clinical information of patients who were diagnosed and treated in multiple tertiary-care academic facilities. MATERIALS AND METHODS: Between February 2007 and April 2015, 95 patients diagnosed with PUNLMP after transurethral resection of bladder (TURB) were included in this study. Age, gender, body mass index, smoking history, the presence or absence of previous history of urothelial neoplasm, the presence or absence of gross hematuria, cytological results at the time of diagnosis, tumor diameter, and multiplicity of tumor were estimated as variablesfor analysis. Cox regression tests were used for identifying predictive factors for recurrence of PUNLMP. RESULTS: Sixty-nine cases of PUNLMP were de novo primary bladder PUNLMPs without known urothelial lesions in the urinary tract, and 26 PUNLMPs were identified on surveillance biopsies of patients with a previous history of urothelial neoplasm. During the follow-up period, recurrences developed in 13 patients (13.7%). Recurrence rates were 4.2% and 9.5% at 12 and 24 months, respectively. On univariate and multivariate Cox regression analyses, previous history of urothelial neoplasm [95% confidence interval (CI): 0.057-0.604, hazard ratio (HR) = 0.185, P = .005] and multiplicity of tumors [95% CI = 0.064-0.584, HR = 0.193, P = .004] were identified as independent predictors for recurrence-free survival of patients with PUNLMP. CONCLUSION: Tumor multiplicity and previous history of urothelial neoplasm are independent prognostic factors forprediction of recurrence of PUNLMP. More careful and closer follow-up should be recommended for PULNMPpatients with tumor multiplicity or a previous history of urothelial neoplasm.	bladder
Obatoclax, a BH3 Mimetic, Enhances Cisplatin-Induced Apoptosis and Decreases the Clonogenicity of Muscle Invasive Bladder Cancer Cells via Mechanisms That Involve the Inhibition of Pro-Survival Molecules as Well as Cell Cycle Regulators.	Several studies by our group and others have determined that expression levels of Bcl-2 and/or Bcl-xL, pro-survival molecules which are associated with chemoresistance, are elevated in patients with muscle invasive bladder cancer (MI-BC). The goal of this study was to determine whether combining Obatoclax, a BH3 mimetic which inhibits pro-survival Bcl-2 family members, can improve responses to cisplatin chemotherapy, the standard of care treatment for MI-BC. Three MI-BC cell lines (T24, TCCSuP, 5637) were treated with Obatoclax alone or in combination with cisplatin and/or pre-miR-34a, a molecule which we have previously shown to inhibit MI-BC cell proliferation via decreasing Cdk6 expression. Proliferation, clonogenic, and apoptosis assays confirmed that Obatoclax can decrease cell proliferation and promote apoptosis in a dose-dependent manner. Combination treatment experiments identified Obatoclax + cisplatin as the most effective treatment. Immunoprecipitation and Western analyses indicate that, in addition to being able to inhibit Bcl-2 and Bcl-xL, Obatoclax can also decrease cyclin D1 and Cdk4/6 expression levels. This has not previously been reported. The combined data demonstrate that Obatoclax can inhibit cell proliferation, promote apoptosis, and significantly enhance the effectiveness of cisplatin in MI-BC cells via mechanisms that likely involve the inhibition of both pro-survival molecules and cell cycle regulators.	bladder
Back pain following instillations of BCG for superficial bladder cancer is not a reactive complication: review of 30 Mycobacterium bovis BCG vertebral osteomyelitis cases.	Mycobacterium bovis Bacillus Calmette-Guérin (BCG) instillations are used in bladder cancer treatment. Adverse effects can occur. Osteoarticular complications are mainly reactive arthritis, but true infections have been described, such as vertebral osteomyelitis. We made a review of M. bovis BCG vertebral osteomyelitis after instillations for bladder cancer using PubMed search. We added three new French cases. Twenty-seven cases of BCG vertebral osteomyelitis had been reported on PubMed. Of the 30 cases, all were male, averaging 73.4 ± 8.7 years old. Median time between diagnosis and first and last instillation was 22.5 and 14 months respectively. Half of vertebral osteomyelitis was thoracic and lumbar in the other half. Sensitivo-motor deficit was present at diagnosis in 42% of cases. Other infectious locations were common, mainly infectious abdominal aortic aneurysms (20%). Rifampicin, ethambutol and isoniazid were the usual therapy. Poor outcomes were reported with 50% of one or more spine surgery. M. bovis BCG vertebral osteomyelitis following bladder instillation for bladder cancer is a rare complication. However, the late onset of back pain after instillations differentiates them from reactive arthritis. Concomitant septic location such as infectious abdominal aortic aneurysms must be known.	bladder
Risk of Bone Fractures Following Urinary Intestinal Diversion: A Population Based Study.	PURPOSE: Patients with bladder cancer who undergo intestinal urinary diversion may be at increased risk for bone fractures thought to be secondary to chronic metabolic acidosis and ensuing bone loss. Our main objective was to assess whether patients who undergo intestinal urinary diversion are at increased risk for fracture. MATERIALS AND METHODS: Patients who underwent intestinal urinary diversion between 1994 and 2014 in Ontario, Canada were identified using linked administrative databases. Patients were categorized as undergoing diversion for bladder cancer or nonbladder cancer causes and matched 4:1 to a healthy cohort. We determined incidence rates of the incidence of fractures per 100 person-years. Multivariable Cox proportional hazards models were used to evaluate the impact of intestinal urinary diversion on the risk of fracture. RESULTS: Overall 4,301 patients with and 907 without bladder cancer underwent intestinal urinary diversion. The fracture incidence rate was significantly greater in the bladder cancer and nonbladder cancer cohorts compared to respective matched controls. In the bladder cancer cohort vs matched controls there were 4.41 vs 2.63 fractures per 100 person-years and in the nonbladder cancer cohort vs matched controls there were 5.67 vs 3.51 fractures per 100 person-years (each p <0.001). On multivariable analysis patients who underwent intestinal urinary diversion for bladder cancer or nonbladder cancer reasons had significantly shorter fracture-free survival compared to the respective matched cohorts (HR 1.48, IQR 1.35-1.63, and HR 1.48, IQR 1.31-1.69, respectively). CONCLUSIONS: Our results demonstrated that regardless of age patients with intestinal urinary diversion are at increased risk for bone fractures compared to the general population. Our findings are in line with previous reports and support the need for bone health monitoring.	bladder
Plasmacytoid Urothelial Carcinoma: An Unusual Variant That Warrants Aggressive Management and Critical Distinction on Transurethral Resections.	Plasmacytoid urothelial carcinoma (PUC) is a variant of infiltrating urothelial carcinoma that is characterized by tumor cells that have striking morphologic resemblance to and immunohistochemical overlap with plasma cells, and that harbors CDH1 mutation. Plasmacytoid urothelial carcinoma can be widely infiltrative and may permeate the urinary bladder in a linitis plastica-like manner and spread along the fascial planes and into the peritoneum. Compared with conventional urothelial carcinoma, PUCs have a greater chance for higher-stage disease, surgical margin positivity, and metastasis at presentation that translate into its poorer outcome. Upstaging of lamina propria-invasive (pT1) tumors diagnosed at transurethral resections is common. Because of its unfavorable behavior, a more aggressive management approach is being recommended for PUC, including consideration for upfront cystectomy in pT1 tumors. Thus, accurate distinction should be made especially on the initial transurethral resection specimens because of the therapeutic and prognostic implications. Awareness of PUC's unique clinical presentation, morphology, and immunohistochemical profile is important to avoid a potential misdiagnosis from its mimics.	bladder
Transcribed ultraconserved region Uc.63+ promotes resistance to cisplatin through regulation of androgen receptor signaling in bladder cancer.	Cisplatin (CDDP)‑based combination chemotherapy is the standard for muscle‑invasive bladder cancer (MIBC). However, nearly all patients undergoing CDDP chemotherapy become refractory due to the development of CDDP resistance. Therefore, clarification of the mechanisms of CDDP resistance is urgently needed. The transcribed ultraconserved regions (T‑UCRs) are a novel class of non‑coding RNAs that are highly conserved across species and are associated with carcinogenesis and cancer progression. In addition, emerging evidence has shown the involvement of androgen receptor (AR) signals in urothelial carcinoma (UC) progression. The aim of the present study was to investigate the expression of transcribed ultraconserved region Uc.63+, and to analyze the effects of Uc.63+ on AR expression and CDDP resistance in UC. Quantitative reverse transcription‑polymerase chain reaction (qRT‑PCR) revealed that the expression of Uc.63+ was higher in UC tissues than that in non‑neoplastic bladder tissues and 15 types of normal tissue. An MTT assay revealed that Uc.63+ was involved in cell proliferation. Western blotting demonstrated that the expression of AR was disrupted by the overexpression or knockdown of Uc.63+ in AR‑positive UMUC3 cells. Furthermore, knockdown of Uc.63+ increased sensitivity to CDDP in UMUC3 cells. Conversely, overexpression of Uc.63+ had no effect on CDDP sensitivity in AR‑negative RT112 cells. Additionally, we observed that the expression of Uc.63+ was increased in CDDP‑resistant UMUC3 cells (UMUC3‑CR) in comparison with that in parental UMUC3 cells. Knockdown of Uc.63+ re‑sensitized the UMUC3‑CR cells to CDDP. These results indicated that Uc.63+ may be a promising therapeutic target to overcome CDDP resistance in UC.	bladder
The role of metastatic burden in cytoreductive/consolidative radical cystectomy.	PURPOSE: To describe our institutional experience with cytoreductive/consolidative radical cystectomy (CCRC) for metastatic urothelial carcinoma (UC) and to investigate clinicopathologic features predicting prolonged cancer specific survival (CSS) following CCRC. METHODS: We performed IRB-approved review of our cystectomy database, and identified 43 patients with metastatic UC who underwent CCRC. Baseline demographics, chemotherapy regimen, clinicopathologic features, and perioperative complications were collected. Progression-free survival (PFS) and CSS were estimated from the time of CCRC. Univariate and multivariate Cox regression models were used to identify predictors of improved CSS after CCRC. RESULTS: Of the 43 patients, 32 (74.4%) had clinical evidence of distant metastases, while 11 harbored occult metastases on the surgical specimen. The most common site of metastasis was the retroperitoneal lymph nodes, found in 30 patients. Solitary metastases were found in 22 patients (51.1%). Forty-one (95%) patients received chemotherapy prior to CCRC. Disease progression was detected in 35 patients after CCRC (median PFS 5.9 months), and 34 died of metastatic cancer (median CSS 12.3 months). On multivariate analysis, patients with solitary metastases were found to have improved CSS compared to those with multiple metastases (HR 2.62, 95% CI 1.16-5.90, p = 0.02), with median CSS of 26.0 months vs. 7.9 months (p < 0.001). Median postoperative length of stay was 10 days. Overall, 56% suffered postoperative complications, including one perioperative mortality. CONCLUSIONS: CCRC is feasible in the setting of metastatic UC. Patients with solitary metastasis demonstrated longer CSS than those with multiple metastases, and should be considered candidates for future trials evaluating the role of CCRC for metastatic UC.	bladder